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Preimplantation Genetic Testing for Structural Rearrangements
Published in Darren K. Griffin, Gary L. Harton, Preimplantation Genetic Testing, 2020
Eventually, FISH and STR-typing were replaced by comprehensive cytogenetic techniques such as aCGH and SNP-arrays. It thus became possible for the first time to detect aneuploidy and segmental imbalances simultaneously in a single biopsy material from an embryo [70,71]. The first technique that was developed for comprehensive analysis of embryos was comparative genomic hybridization (CGH), first introduced in molecular cytogenetics in 1992 to detect somatic mutations in cancer cells [72]. When applied to biopsied embryo cells, samples were amplified by whole-genome amplification (WGA) followed by co-hybridization of differentially labeled test and reference DNA on to normal metaphase chromosomes where analysis takes place on the microscope [73]. However, the resolution of this technique proved to be low (10–25 Mb) [70,74]; it is also laborious and time consuming. Malmgren et al. in 2002 analyzed 94 blastomeres from 7 couples carrying structural chromosome rearrangements, and the results were rechecked using FISH [70]. The confirmation rate between CGH and FISH was not satisfactory, possibly due to a high degree of mosaicism (∼100%) and the presence of chaotic complements in the cleavage-stage embryos.
Central nervous system: Paediatric and neurodevelopmental disorders
Published in Angus Clarke, Alex Murray, Julian Sampson, Harper's Practical Genetic Counselling, 2019
One reason for the early progress in identifying genes responsible for neurodevelopmental disorders, and the dysmorphic syndromes that may also be associated with cognitive impairment, is that clinical geneticists would often be involved in the diagnostic assessment of such patients. As a group, clinical geneticists had early access to the laboratory facilities required to locate the genes through linkage studies or molecular cytogenetics. The resulting progress, and the improved understanding of these disorders, is now informing the development of rational approaches to treatment. The identification of the relevant gene has often been a first essential step to the identification of the protein implicated in the mechanism of disease; this has then enabled the development of possible therapeutic strategies.
Molecular Biology
Published in John C Watkinson, Raymond W Clarke, Louise Jayne Clark, Adam J Donne, R James A England, Hisham M Mehanna, Gerald William McGarry, Sean Carrie, Basic Sciences Endocrine Surgery Rhinology, 2018
Michael Kuo, Richard M. Irving, Eric K. Parkinson
During normal cell division, DNA replication is achieved by the separation of the two strands by DNA helicase. Each separated single strand then acts as a template for polymerization, catalyzed by DNA polymerase, of nucleotides forming a new complementary strand and thus double-stranded DNA identical to the original dsDNA. As each daughter DNA consists of one original and one newly synthesized DNA strand, the process is known as semi-conservative replication. The specificity of the complementary relationship between the nucleotides on each strand forms the basis for many techniques of modern molecular biology and molecular cytogenetics.1 The accuracy with which DNA replication takes place is remarkable with an estimated error rate of less than one in 109 nucleotide additions. Such accuracy is of vital importance to the individual as a permanent change in DNA, or mutation may cause inactivation of a gene essential to cell survival or cell cycle control. The high fidelity of DNA sequence replication is achieved by unidirectional 5’-to-3’ direction of DNA replication, a rigorous DNA proofreading mechanism that detects mismatched DNA and efficient DNA repair pathways that excise and repair DNA damage. Failure of these mechanisms, such as is encountered in xeroderma pigmentosum, Fanconi’s anaemia and ataxia telangiectasia, leads to accumulation of DNA replication errors and a high incidence of malignancies.
The successful strategy of comprehensive pre-implantation genetic testing for beta-thalassaemia–haemoglobin E disease and chromosome balance using karyomapping
Published in Journal of Obstetrics and Gynaecology, 2022
Sirivipa Piyamongkol, Suchada Mongkolchaipak, Pimlak Charoenkwan, Rungthiwa Sirapat, Wanwisa Suriya, Tawiwan Pantasri, Theera Tongsong, Wirawit Piyamongkol
Amplified MDA samples were tested for aSNP using an Illumina HumanKaryomap-12 DNA Analysis Kit (Bio-Active Co. Ltd., Bangkok, Thailand) by the manufacturer’s instructions (Handyside et al. 2010). SNP genotyping information was analysed using BlueFuse Multi software (Illumina, Inc., San Diego, CA) for karyomapping analysis and molecular cytogenetics. Haplotyping analysis of the couples together with a close blood relative as references can be used to reveal the potential inheritance of unaffected or affected genes in the embryos. In addition, SNP genotyping information provides CNV details of every chromosome. Results were collected and compared with the mutation analysis.